A prevalent form of relapse in addiction is caused by exposure to cues or contexts formerly paired with drug delivery. The ability of drug-paired conditioned stimuli (CSs) to increase incentive motivation, or "craving", indicates that the rewarding properties of drug exposure can be associated with CSs predicting their delivery through a Pavlovian incentive learning process. Recent research raises the possibility that, as a consequence of neuroadaptations resulting from repeated drug exposure, the ability of CSs to compel reward-seeking behavior is enhanced among former drug users. To fully explore this hypothesis, a greater understanding is necessary of the motivational processes that underlie Pavlovian influences on reward-seeking behavior generally, as well as the effects of repeated drug exposure on these processes. This proposal examines the effect of drug sensitization on the ability of Pavlovian cues to influence reward-seeking behavior, with the overall goal of characterizing the motivational processes that underlie the enhanced responsiveness to reward-associated CSs in amphetamine-sensitized rats. The proposed experiments make use of Pavlovian-instrumental transfer (PIT) paradigm to assess the role of outcome saliency and general arousal in determining the choice and intensity of instrumental actions during PIT. These experiments are important for understanding the process through which drug exposure alters the influence of reward-predictive cues on reward-seeking behavior, and will serve as the basis for further research into the neural systems and molecular mechanisms underlying Pavlovian incentive processes and their modulation by exposure to drugs of abuse. Furthermore, these studies will be important in devising therapeutic strategies to treat relapse based on an understanding of the relevant factors that underlie Pavlovian influences on reward-seeking behavior. PUBLIC HEALTH RELEVANCE: The proposed research addresses behavioral processes that are central to substance abuse disorders, and thus is highly relevant to public health. Furthermore, the research findings may be useful in devising therapeutic strategies to prevent relapse caused by re-exposure to drug-associated cues.